1247874-19-6
Chemical Structure
PF-477736 hydrochloride
- CAS No.: 1247874-19-6
- Formula:C22H27Cl2N7O2
- Molecular Weight:492.40
InChIKey: RXRFKHCZZSOCOS-JQDLGSOUSA-N
SMILES: O=C1C2=C3C(C=NN1)=C(C4=CN(C)N=C4)NC3=CC(NC([C@@H](C5CCCCC5)N)=O)=C2.Cl.Cl
Biological Activity: PF-477736 (hydrochloride) is an ATP-competitive Chk1 inhibitor (Ki 0.49 nM) that also inhibits CK2A1, PKCA, and Akt1, and is a broad-spectrum kinase inhibitor[1][2].PF-477736 induces apoptosis via PARP cleavage, caspase-3/7 activation, caspase-independent death, BAX and PUMA upregulation, H2AX phosphorylation, DNA fragmentation, and Chk1 proteasomal degradation, while inhibiting proliferation and preventing mitotic entry[1][2].PF-477736 demonstrates selective synthetic lethality in LIMD1-deficient cells, efficacy in subcutaneous xenograft models of LIMD1-deficient tumors, and anti-proliferative activity against leukemia and lymphoma cell lines[1].PF-477736 induces DNA double-strand breaks and activates the ATM-p53-p21 axis, and sensitizes CHK1i-insensitive neuroblastoma cells to apoptosis with ATM or DNA-PK inhibitors[2].PF-477736 can be used for the research of non-small cell lung cancer, leukemia, lymphoma, and neuroblastoma[1][2].
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PF-477736 hydrochloride | PF-477736 (hydrochloride) is an ATP-competitive Chk1 inhibitor (Ki 0.49 nM) that also inhibits CK2A1, PKCA, and Akt1, and is a broad-spectrum kinase inhibitor.PF-477736 induces apoptosis via PARP cleavage, caspase-3/7 activation, caspase-independent death, BAX and PUMA upregulation, H2AX phosphorylation, DNA fragmentation, and Chk1 proteasomal degradation, while inhibiting proliferation and preventing mitotic entry.PF-477736 demonstrates selective synthetic lethality in LIMD1-deficient cells, efficacy in subcutaneous xenograft models of LIMD1-deficient tumors, and anti-proliferative activity against leukemia and lymphoma cell lines.PF-477736 induces DNA double-strand breaks and activates the ATM-p53-p21 axis, and sensitizes CHK1i-insensitive neuroblastoma cells to apoptosis with ATM or DNA-PK inhibitors.PF-477736 can be used for the research of non-small cell lung cancer, leukemia, lymphoma, and neuroblastoma. | |||||||||||||||||||||
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References
- [1]. Davidson K, et al. Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes. Cell death & disease. 2021 Nov 11;12(11):1075.
- [2]. Ando K, et al. Co-Inhibition of the DNA Damage Response and CHK1 Enhances Apoptosis of Neuroblastoma Cells. International journal of molecular sciences. 2019 Jul 29;20(15):3700.
